Mix of Kudos and Caution for Fecal DNA Test

Approval and imminent Medicare coverage of a DNA screening test for colorectal cancer generally received props from clinicians and researchers, who nonetheless cited continued patient aversion as the biggest obstacle to screening.

On Tuesday the FDA approved the Cologuard test and, at the same time, the Centers for Medicare and Medicaid Services (CMS) announced proposed Medicare coverage of the test. The unprecedented parallel review by the two agencies represented the first step in a pilot program to expedite approval and coverage of selected devices.

Andrew T. Chan, MD, PhD, a GI cancers specialist at Massachusetts General Hospital in Boston, called the approval an "important new development in colorectal cancer screening."

"Although screening by colonoscopy is still widely considered the gold standard and the best test for prevention of colorectal cancer, this DNA test provides an appropriate and reasonable alternative for those patients who prefer a less invasive screening option," Chan told MedPage Today in an email.

Robert Wergin, MD, president-elect of the American Academy of Family Physicians, welcomed the test as another option for average-risk patients who refuse or cannot afford colonoscopy.

"This may help us increase screening rates," said Wergin. "The U.S. Preventive Services Task Force has included fecal DNA in their research plan for their update of colorectal cancer screening. We look forward to their findings."

The fecal immunochemical test (FIT) represented an advance over guaiac fecal occult blood testing, and the DNA test has demonstrated the ability to detect more advanced adenomatous polyps and colon cancers as compared with FIT, said Howard Hochster, MD, a GI cancers specialist at Yale Cancer Center. Deciding how to use the test is another issue.

"This test will pick up more colon cancers and adenomas than FIT but also is less [specific], so lower predictive value," said Hochster. "However, it should lead to more colonoscopies for people with large adenomas or actual colon cancer."

He added that the DNA test "should not be used after FIT but instead of FIT."

In the setting of a negative stool test, the DNA test reduced the risk of colon cancer from 0.7% to 0.06% as compared with 0.18% with FIT.

"Use [of the DNA test] after a negative test is really not worth it," said Hochster. "It would only make sense if CMS wishes to save money because FIT may be substantially cheaper."

A spokesperson for the American Gastroenterological Association (AGA) emphasized that the DNA test -- like other stool tests -- is for detection only, not prevention of colon cancer.

"In the recent New England Journal of Medicine article, the stool DNA test only detected 42% of advanced precancerous lesions in the colon," said Rajeev Jain, MD, of Texas Digestive Disease Consultants in Dallas. "In my opinion, stool DNA testing may be considered in patients who decline screening colonoscopy, as colonoscopy offers both colon cancer prevention and early detection."

How the DNA test performs in clinical practice -- as opposed to a clinical trial -- also remains unclear, said Deborah A. Fisher, MD, of Duke University.

"What is not known is how the test performs as part of a screening program in which negative tests are repeated at regular intervals, positive tests are further evaluated by colonoscopy, and patient adherence is a factor," said Fisher, also an AGA spokesperson.

The CMS coverage proposal for the test -- once every 3 years -- is open to question, Fisher continued. By comparison, a wealth of data has accumulated regarding the longitudinal performance of FIT and FOBT, appropriate screening interval, and performance in a screening program.

"Therefore, it is not clear that it is a 'better' screening strategy than those currently in use," she added. "Nonetheless, this test appears to be a reasonable strategy for screening individuals who are average risk for colorectal cancer and are not experiencing GI symptoms."

Only when experience with the test in clinical practice has accumulated will the true role and value of the DNA test be known, said Eduardo Vilar-Sanchez, MD, PhD, of the University of Texas M.D. Anderson Cancer Center in Houston.

"We are still in the very earliest steps," said Vilar-Sanchez. "I think this is a major step in the screening for colon cancer. I foresee that it might substitute for FOBT and FIT. However, I am cautious because economics play a big role in these decisions. The study [published in NEJM] did not include a cost-effectiveness study, which is something that has to be performed."

Another limitation of the pivotal study is that the DNA test and FIT were performed at a single point in time, whereas in clinical practice, screening tests are performed on an ongoing basis, he added.

As with FOBT and FIT, the DNA test requires a stool sample, which has turned off many patients to screening for colorectal cancer. Similarly, patients have avoided screening colonoscopy in droves. A recent study by the CDC showed that more than a third of eligible adults had not been screened for colorectal cancer.

"Our greatest challenge right now is the number of individuals who are not screened," said Wergin, who practices in Milford, Neb.

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